Identification of Prognostic Genes in Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35300146", "kind": "science-record", "revision": 4, "content_hash": "sha256:89082ea152ea56a0dd7d6ab24bd45e40d88c1a79de388f57a297bf889d704b05", "created_at": "2026-11-01T18:14:05Z", "updated_at": "2026-11-01T22:06:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Prognostic Genes in Hepatocellular Carcinoma.", "doi": "10.2147/IJGM.S347535", "pmid": "35300146", "authors": ["Wenhui Bai", "Li Cheng", "Liangkun Xiong", "Maoming Wang", "Hao Liu", "Kaihuan Yu", "Weixing Wang"], "journal": "International journal of general medicine", "year": 2022, "abstract": "Background: Previous studies have demonstrated the important role of tumor stem cells (TSCs) in the development of hepatocellular carcinoma (HCC); however, TSC-related genetic markers have not been investigated.\nAim: The aim of the present study was to identify stem cell-related signature genes to predict the prognosis of HCC, using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.\nMethods: In total, 423 liver HCC tissue samples, including 373 tumor and 50 adjacent normal tissue samples from TCGA, and 115 primary tumor and 52 adjacent non-tumor tissue samples from the GEO GSE76427 database, were used in the present study. The non-negative matrix factorization (NMF) algorithm, t-distributed stochastic neighbor embedding (t-SNE) algorithm and Cox regression analysis were combined for model construction and validation.\nResults: Overall, six clusters were identified using the NMF and t-SNE algorithms with 470 stem cell-related genes. The results demonstrated that patients in cluster 5 had the worst prognosis. For multivariate Cox survival analysis, 15 genes with optimal lambda values were chosen and eight genes were incorporated into the final regression model using the optimal Akaike information criterion value. Validation of the risk model using the aforementioned eight signature genes demonstrated the models strong reliability and stable predictive performance.\nConclusion: The results of the present study indicated that the eight-gene (Hes family BHLH transcription factor 5, KIT ligand, methyltransferase-like 3, proteasome 26S subunit non-ATPase 1, Ras-related protein Rab-10, treacle ribosome biogenesis factor 1, YTH N6-methyladenosine RNA binding protein 2 and Zinc Finger CCCH-Type Containing 13) signature constructed by the model may be reliable in predicting the prognosis of patients with HCC.", "claims": [{"id": "claim-method", "statement": "The non-negative matrix factorization (NMF) algorithm, t-distributed stochastic neighbor embedding (t-SNE) algorithm and Cox regression analysis were combined for model construction and validation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35300146", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The non-negative matrix factorization (NMF) algorithm, t-distributed stochastic neighbor embedding (t-SNE) algorithm and Cox regression analysis were combined for model construction and validation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Clinical, RNA-sequencing (seq) and pathological data were provided by the Genomic Data Commons Data Portal.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35300146", "locator": "sections[3] \"Data Collection\" paragraph 2", "quote": "Clinical, RNA-sequencing (seq) and pathological data were provided by the Genomic Data Commons Data Portal."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results of the present study indicated that the eight-gene (Hes family BHLH transcription factor 5, KIT ligand, methyltransferase-like 3, proteasome 26S subunit non-ATPase 1, Ras-related protein Rab-10, treacle ribosome biogenesis factor 1, YTH N6-methyladenosine RNA binding protein 2 and Zinc Finger CCCH-Type Containing 13) signature constructed by the model may be reliable in predicting the prognosis of patients with HCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35300146", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "The results of the present study indicated that the eight-gene (Hes family BHLH transcription factor 5, KIT ligand, methyltransferase-like 3, proteasome 26S subunit non-ATPase 1, Ras-related protein Rab-10, treacle ribosome biogenesis factor 1, YTH N6-methyladenosine RNA binding protein 2 and Zinc Finger CCCH-Type Containing 13) signature constructed by the model may be reliable in predicting the prognosis of patients with HCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results of the present study indicated that the eight-gene (Hes family BHLH transcription factor 5, KIT ligand, methyltransferase-like 3, proteasome 26S subunit non-ATPase 1, Ras-related protein Rab-10, treacle ribosome biogenesis factor 1, YTH N6-methyladenosine RNA binding protein 2 and Zinc Finger CCCH-Type Containing 13) signature constructed by the model may be reliable in predicting the prognosis of patients with HCC.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35300146"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE76427"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE76427"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35300146", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S347535", "sha256": "sha256:a61a09eb817915b14fb49af434c3ee4e45b75d3a28a8d4782490268320914bc5", "bytes": 29753, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S347535", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8923701", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE76427", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76427", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76427", "version": null, "note": "Clinical, RNA-sequencing (seq) and pathological data were provided by the Genomic Data Commons Data Portal.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Clinical, RNA-sequencing (seq) and pathological data were provided by the Genomic Data Commons Data Portal.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2011285", "GSM2011286", "GSM2011287", "GSM2011288", "GSM2011289", "GSM2011290", "GSM2011291", "GSM2011292", "GSM2011293", "GSM2011294", "GSM2011295", "GSM2011296", "GSM2011297", "GSM2011298", "GSM2011299", "GSM2011300", "GSM2011301", "GSM2011302", "GSM2011303", "GSM2011304", "GSM2011305", "GSM2011306", "GSM2011307", "GSM2011308", "GSM2011309", "GSM2011310", "GSM2011311", "GSM2011312", "GSM2011313", "GSM2011314", "GSM2011315", "GSM2011316", "GSM2011317", "GSM2011318", "GSM2011319", "GSM2011320", "GSM2011321", "GSM2011322", "GSM2011323", "GSM2011324", "GSM2011325", "GSM2011326", "GSM2011327", "GSM2011328", "GSM2011329", "GSM2011330", "GSM2011331", "GSM2011332", "GSM2011333", "GSM2011334", "GSM2011335", "GSM2011336", "GSM2011337", "GSM2011338", "GSM2011339", "GSM2011340", "GSM2011341", "GSM2011342", "GSM2011343", "GSM2011344", "GSM2011345", "GSM2011346", "GSM2011347", "GSM2011348", "GSM2011349", "GSM2011350", "GSM2011351", "GSM2011352", "GSM2011353", "GSM2011354", "GSM2011355", "GSM2011356", "GSM2011357", "GSM2011358", "GSM2011359", "GSM2011360", "GSM2011361", "GSM2011362", "GSM2011363", "GSM2011364", "GSM2011365", "GSM2011366", "GSM2011367", "GSM2011368", "GSM2011369", "GSM2011370", "GSM2011371", "GSM2011372", "GSM2011373", "GSM2011374", "GSM2011375", "GSM2011376", "GSM2011377", "GSM2011378", "GSM2011379", "GSM2011380", "GSM2011381", "GSM2011382", "GSM2011383", "GSM2011384", "GSM2011385", "GSM2011386", "GSM2011387", "GSM2011388", "GSM2011389", "GSM2011390", "GSM2011391", "GSM2011392", "GSM2011393", "GSM2011394", "GSM2011395", "GSM2011396", "GSM2011397", "GSM2011398", "GSM2011399", "GSM2011400", "GSM2011401", "GSM2011402", "GSM2011403", "GSM2011404", "GSM2011405", "GSM2011406", "GSM2011407", "GSM2011408", "GSM2011409", "GSM2011410", "GSM2011411", "GSM2011412", "GSM2011413", "GSM2011414", "GSM2011415", "GSM2011416", "GSM2011417", "GSM2011418", "GSM2011419", "GSM2011420", "GSM2011421", "GSM2011422", "GSM2011423", "GSM2011424", "GSM2011425", "GSM2011426", "GSM2011427", "GSM2011428", "GSM2011429", "GSM2011430", "GSM2011431", "GSM2011432", "GSM2011433", "GSM2011434", "GSM2011435", "GSM2011436", "GSM2011437", "GSM2011438", "GSM2011439", "GSM2011440", "GSM2011441", "GSM2011442", "GSM2011443", "GSM2011444", "GSM2011445", "GSM2011446", "GSM2011447", "GSM2011448", "GSM2011449", "GSM2011450", "GSM2011451"], "sample_count": 167, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Microarray expression data for tumor and adjacent non-tumor tissues from hepatocellular carcinoma patients", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE76427 not downloaded", "asset:data:geo:GSE76427 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The non-negative matrix factorization (NMF) algorithm, t-distributed stochastic neighbor embedding (t-SNE) algorithm and Cox regression analysis were combined for model construction and validation."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE76427"], "resolved_accessions": ["GSE76427"], "statements": ["Clinical, RNA-sequencing (seq) and pathological data were provided by the Genomic Data Commons Data Portal."], "basis": "The paper names GSE76427 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35300146", "data:geo:GSE76427"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE76427"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:38:26Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 8605, "completion_tokens": 1259, "cached_tokens": 188}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35300146", "type": "paper", "label": "pmid:35300146"}, {"id": "source:pmid:35300146", "type": "manuscript", "label": "PMID 35300146 full text"}, {"id": "data:geo:GSE76427", "type": "dataset", "label": "GEO GSE76427"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35300146", "type": "paper", "label": "pmid:35300146"}, {"id": "source:pmid:35300146", "type": "manuscript", "label": "PMID 35300146 full text"}, {"id": "data:geo:GSE76427", "type": "dataset", "label": "GEO GSE76427"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35300146", "type": "extraction", "used": ["source:pmid:35300146"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE76427", "type": "accession_resolution", "used": ["data:geo:GSE76427"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35300146", "parent_hash": "sha256:5b6e09e4dd96ea12b71054e6f0beb02f3f0da0e8e7337a16cb9a3334c58c8b4c", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE76427 licence not read", "asset:data:geo:GSE76427 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "methylation_array", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["CIBERSORT, quanTIseq, xCell, MCP-counter and EPIC algorithms (https://timer.cistrome.org/). A"], "order_basis": "paper_text_order:3675", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The non-negative matrix factorization (NMF) algorithm, t-distributed stochastic neighbor embedding (t-SNE) algorithm and Cox regression analysis were combined for model construction and validation."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}